医药行业科技成果产业化的风险控制

医药行业科技成果产业化与其他行业科技成果转化相比具有更高的风险，转化能力也是最低的，因此，对其从事前、事中、事后三方面加强风险控制具有重要的观实意义。     

大鼠肾上腺髓质增生MRI与病理的对比研究

目的通过 MRI 研究大鼠肾上腺髓质增生(AMH)的信号特征,并与病理结果对比,探讨 MRI 诊断大鼠 AMH 的可能性。方法雄性 SD 大鼠60只,依体重大小,采取随机排列表法随机分为 A、B、C 实验组,皮下注射利血平0.4 mg·kg~(-1)·d~(-1);a、b、c 对照组,皮下注射等量生理盐水,每组10只。A、a,B、b,C、c 组分别连续注射40、60和80 d,行肾上腺 MR 扫描,并和病理研究作对照。结果注射60 d 后 B 组髓质百分数(34.3±5.8)%高于 b 组(25.7±8.9)%(t=2.462,P<0.05),C 组(36.4±7.8)%也高于 c 组(24.8±7.9)%(t=3.104,P<0.01),利血平注射60 d 后 AMH 造模成功;MR 下 B 和 b 组、C 和 c 组肾上腺体积分别为(50.7±14.1)和(41.1±11.0)、(52.7±10.5)和(40.4±10.7)mm~3,差异有统计学意义(t 值分别为2.352、3.442,P 值分别<0.05、<0.01);MR 下中心髓质区 T_2WI 信号 B 组高于 b 组(Z=-3.786,P<0.01)、C 组高于 c 组(Z=-3.570,P<0.01);光学显微镜(简称光镜)下见 B 和 C 组髓质明显增厚,细胞数增多、密集,呈实质性片状或条索状分布,形成细胞巢;实验组部分大鼠 T_1WI 下外周皮质信号明显增高,光镜下见束状带增生,细胞呈空泡状肥大,富含脂质。结论 MRT_2WI 中心髓质区信号增高及 T_1WI 外周皮质高信号可能对于诊断大鼠肾上腺髓质增生有意义。     

核仁形成区嗜银蛋白定量对结肠癌前病变的监测作用

应用银染技术,对24例结肠腺癌Ⅱ级不典型增生,30例绒毛状腺瘤,14例绒毛状腺瘤Ⅲ级不典型增生和29例高分化管状腺癌进行银染核仁形成区嗜银蛋白(Ag-NORs)定量研究,观察Ag-NORs数量、形态、大小和分布在结肠肿瘤交界性病变中的表达.提示Ag-NORs四项指标定量研究对结肠脉瘤,特别是Ⅲ级不典型增生与绒毛状腺瘤之结肠癌前病变有较好的监测作用.     

利浦松软膏防治烧伤创面瘢痕120例疗效观察

目的 :观察利浦松软膏防治烧伤创面瘢痕的疗效。方法 :将利浦松软膏涂擦于烧伤愈合创面 ,观察瘢痕生长情况。结果 :12 0例烧伤病人创面显效 32例 ,有效 72例 ,无效 16例。结论 :利浦松软膏用于防治烧伤创面瘢痕疗效显著 ,方法简单 ,便于推广应用     

20q13.2 Amplification in intraductal hyperplasia adjacent to in situ and invasive ductal carcinoma of the breast

The 20q13 region harboring recently described putative oncogenes is frequently amplified in invasive ductal carcinoma (IDC). The aim of this study was to examine the 20q13 copy number in intraduct hyperplasia (IH), atypical duct hyperplasia (ADH), and ductal carcinoma in situ (DCIS) adjacent to IDC. In 5 patients, comparative genomic hybridization (CGH) after laser microdissection revealed 20q13 amplification in four of five cases of IH, in all of three cases of IH with atypia, all five of DCIS, and all five of IDC. Fluorescence in situ hybridization (FISH) confirmed the amplification at 20q13.2 in IH in the two specimens analyzed. The amplification rate, however, was higher in DCIS and IDC. In phenotypically normal ductal epithelium normal values were found for 20q13 copy number by FISH (n=2) and CGH (n=5). Although the number of cases presented here is small, our results suggest that mutations in the 20q13.2 region in IH may be associated with accelerated proliferation and hyperplasia of the ductal epithelium. Progression to DCIS and ICD is accompanied by a further increase in the 20q13.2 copy number. Received: 17 March 1999 / Accepted: 22 June 1999     

Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting.     

Dermatoglyphics in Congenital Adrenal Hyperplasia (CAH)

Dermatoglyphic findings were compared in 42 patients (32 females, 10 males) with Congenital Adrenal Hyperplasia (CAH) and 110 normal controls (70 females, 40 males). In CAH males, an excess of whorls (p less than 0.001), an increased total finger ridge count (p less than 0.05), and an increased frequency of patterns in the fourth interdigital area (p less than 0.025) was found. A main line A terminating high in the hypothenar area (p less than 0.05), and a missing c-triradius or an abortive main line C (p less than 0.05) was observed in CAH females. Both sexes displayed an increase in the frequency of small radially directed hypothenar patterns (p less than 0.05) and sydney lines (p less than 0.01).     

Central atypical papillomas of the breast: a clinicopathological study of 119 cases

The clinicopathological features of central intraductal papillomas of the breast presenting with florid usual ductal hyperplasia or atypical ductal hyperplasia (ADH) were analyzed in a retrospective series of 119 patients, whose lesions were sent to the Armed Forces Institute of Pathology from 1976 to 1990. After histological review considering predefined morphological and quantitative criteria, the 119 central papillomas were classified into 22 papillomas with florid usual ductal hyperplasia (18%), 40 papillomas with focal atypia (34%), 24 atypical papillomas (20%) and 33 carcinomas arising in a papilloma (28%). After a median period of follow-up of 110 months, 16 recurrences (5 papillomas, 2 carcinomas arising in a papilloma, 4 ductal carcinomas in situ, 5 invasive carcinomas) occurred. No statistically significant difference was observed in relation to recurrence for the various categories of papillomas. The presence of epithelial hyperplasia, ADH or lobular neoplasia in the surrounding breast as well as infarction of the papilloma were significant predictive factors of recurrence (P=0.02 and P=0.005, respectively, log-rank test). The main reason for the observed low rate of significant recurrences in this series was that epithelial atypia (whether comprising 20% or 60% of the papillary lesion) was, in most of the cases, localized in a confined lesion that was completely excised.     

caspase-3、bcl-2蛋白在非霍奇金淋巴瘤组织的表达及其与细胞凋亡和增殖的关系

目的探讨caspase-3、bcl-2蛋白在非霍奇金淋巴瘤(NHL)发生、发展中的可能作用及相互关系.方法应用TdT介导的dUTP缺口末端标记(TUNEL)技术和免疫组织化学链霉素抗生物素-过氧化酶(SP)法,检测5例反应性增生淋巴组织和119例NHL组织中的细胞凋亡和增殖细胞核抗原(PCNA)、caspase-3、bcl-2蛋白的表达水平.结果 caspase-3和bcl-2在119例NHL中表达的阳性率分别为86.6%(103例)和53.8%(64例).二者在良、恶性淋巴组织中的表达方式相反在反应性增生淋巴滤泡中心caspase-3高表达而bcl-2阴性表达,滤泡套区caspase-3阴性表达而bcl-2高表达;在肿瘤性滤泡中心bcl-2常高表达而caspase-3常表达减弱或不表达;在NHL中二者的表达与肿瘤恶性度呈相反关系,高度恶性组中caspase-3的表达(44.4%)高于低度恶性组(23.7%,P<0.01),而B细胞性淋巴瘤中bcl-2的表达(42.6%)低于低度恶性组(75.5%,P<0.01);caspase-3的表达与凋亡指数呈正相关(r=0.512, P <0.01)),bcl-2的表达与凋亡指数呈负相关(r=-0.436, P<0.01).此外,NHL的凋亡指数与增殖指数呈显著正相关(r=0.710, P<0.01).结论 caspase-3可能参与了NHL的凋亡调节机制.caspase-3和bcl-2蛋白在良、恶性淋巴组织中常呈现相反的表达方式,提示二者在淋巴细胞增殖动力学调节中可能存在着密切联系.     

An intrauterine progesterone contraceptive system (52 mg) used in pre- and peri-menopausal patients with endometrial hyperplasia

An intrauterine progesterone contraceptive system (IPCS) (52 mg) was inserted in 25 women with cystic endometrial hyperplasia. Among these women, 11 complained of heavy climacteric symptoms and also received an oestrogen replacement therapy consisting of conjugated oestrogens (0.625 mg/day) administered cyclically for 3 out of 4 wk. Prior to the therapy and after 6 mth of treatment, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oestrone (E1) and oestradiol (E2) plasma levels were measured and endometrial histology was evaluated. In the women receiving IPCS treatment alone, there were no significant changes in FSH, LH, PRL, E1 and E2 plasma levels. However, there were remarkable changes found in their endometrial histology. In the remaining women receiving both treatments there was a sharp decrease in FSH and LH plasma levels and an increase in E1 and E2 plasma levels, while the prolactin levels remained unchanged. With the exception of two of these women, the endometrial histology changed remarkably. The endometrial morphology of the two exceptions remained unchanged. All climacteric symptoms disappeared after the administration of both IPCS and the oestrogen replacement therapy. The remarkable changes which did occur in the endometrial histology resulted in a less active glandular epithelium and stromal decidual formation, thus proving a useful effect of treatment.